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Details

Stereochemistry ACHIRAL
Molecular Formula C13H14N6O
Molecular Weight 270.2904
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of VOXTALISIB

SMILES

CCn1c2c(cc(-c3cc[nH]n3)c1=O)c(C)[nH]c(=N)n2

InChI

InChIKey=RGHYDLZMTYDBDT-UHFFFAOYSA-N
InChI=1S/C13H14N6O/c1-3-19-11-8(7(2)16-13(14)17-11)6-9(12(19)20)10-4-5-15-18-10/h4-6H,3H2,1-2H3,(H,15,18)(H2,14,16,17)

HIDE SMILES / InChI

Molecular Formula C13H14N6O
Molecular Weight 270.2904
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
Curator's Comment:: Description was created based on several sources, including http://www.selleckchem.com/products/XL765(SAR245409).html https://www.ncbi.nlm.nih.gov/pubmed/25300944

Voxtalisib (SAR245409, XL765) is an orally available inhibitor of PI3K and the mammalian target of rapamycin (mTOR), which are frequently activated in human tumors and play central roles in tumor cell proliferation. Exelixis discovered Voxtalisib internally and out-licensed the compound to Sanofi. Voxtalisib is being evaluated by Sanofi as a single agent and in multiple combination regimens in a variety of cancer indications. Clinical trials have included a single agent phase 2 trial in Non-Hodgkin’s lymphoma, combination phase 1b/2 trials with temozolomide in patients with glioblastoma, with letrozole in hormone receptor positive breast cancer, with bendamustine and/or rituximab in lymphoma or leukemia, and a phase 1 trial in combination with a MEK inhibitor. Voxtalisib is a highly selective, potent and reversible ATP-competitive inhibitor of pan-Class I PI3K (α, β, γ, and δ) and mTORC1/mTORC2. It is orally active, highly selective over 130 other protein kinases. In cellular assays, XL765 inhibits the formation of PIP3 in the membrane, and inhibits phosphorylation of AKT, p70S6K, and S6 phosphorylation in multiple tumor cell lines with different genetic alterations affecting the PI3K pathway.

Originator

Curator's Comment:: # Exelixis

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
9.0 nM [IC50]
43.0 nM [IC50]
39.0 nM [IC50]
113.0 nM [IC50]
39.0 nM [IC50]
113.0 nM [IC50]
9.0 nM [IC50]
43.0 nM [IC50]
150.0 nM [IC50]
157.0 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
353 ng/mL
40 mg 2 times / day multiple, oral
dose: 40 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
VOXTALISIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
360 ng/mL
60 mg single, oral
dose: 60 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
VOXTALISIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
416 ng/mL
50 mg 2 times / day multiple, oral
dose: 50 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
VOXTALISIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
541 ng/mL
70 mg single, oral
dose: 70 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
VOXTALISIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
395 ng/mL
40 mg 2 times / day steady-state, oral
dose: 40 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
VOXTALISIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
417 ng/mL
70 mg 1 times / day steady-state, oral
dose: 70 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
VOXTALISIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
549 ng/mL
50 mg 2 times / day steady-state, oral
dose: 50 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
VOXTALISIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
477 ng/mL
60 mg 1 times / day multiple, oral
dose: 60 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
VOXTALISIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
1920 ng × h/mL
40 mg 2 times / day multiple, oral
dose: 40 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
VOXTALISIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
1950 ng × h/mL
60 mg single, oral
dose: 60 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
VOXTALISIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
2110 ng × h/mL
50 mg 2 times / day multiple, oral
dose: 50 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
VOXTALISIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
3840 ng × h/mL
70 mg single, oral
dose: 70 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
VOXTALISIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
1530 ng × h/mL
40 mg 2 times / day steady-state, oral
dose: 40 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
VOXTALISIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
2190 ng × h/mL
70 mg 1 times / day steady-state, oral
dose: 70 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
VOXTALISIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
3390 ng × h/mL
50 mg 2 times / day steady-state, oral
dose: 50 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
VOXTALISIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
3700 ng × h/mL
60 mg 1 times / day multiple, oral
dose: 60 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
VOXTALISIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
2.72 h
40 mg 2 times / day multiple, oral
dose: 40 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
VOXTALISIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
3.5 h
60 mg single, oral
dose: 60 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
VOXTALISIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
4.33 h
50 mg 2 times / day multiple, oral
dose: 50 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
VOXTALISIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
4.55 h
70 mg single, oral
dose: 70 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
VOXTALISIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
2.29 h
40 mg 2 times / day steady-state, oral
dose: 40 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
VOXTALISIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
3.04 h
70 mg 1 times / day steady-state, oral
dose: 70 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
VOXTALISIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
4.2 h
50 mg 2 times / day steady-state, oral
dose: 50 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
VOXTALISIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
3.8 h
60 mg 1 times / day multiple, oral
dose: 60 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
VOXTALISIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
120 mg 2 times / day multiple, oral
Highest studied dose
Dose: 120 mg, 2 times / day
Route: oral
Route: multiple
Dose: 120 mg, 2 times / day
Sources: Page: p.2447
unhealthy, ADULT
n = 7
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: FASTED
Population Size: 7
Sources: Page: p.2447
DLT: Hypophosphatemia, Decreased appetite...
Other AEs: Hepatic enzyme increased...
Dose limiting toxicities:
Hypophosphatemia (grade 3, 14.3%)
Decreased appetite (grade 3, 14.3%)
Other AEs:
Hepatic enzyme increased (42.9%)
Sources: Page: p.2447
40 mg 2 times / day multiple, oral
MTD
Dose: 40 mg, 2 times / day
Route: oral
Route: multiple
Dose: 40 mg, 2 times / day
Sources: Page: p.4
unhealthy, ADULT
n = 6
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 6
Sources: Page: p.4
DLT: Fatigue...
Dose limiting toxicities:
Fatigue (grade 3, 16.7%)
Sources: Page: p.4
50 mg 2 times / day multiple, oral
MTD
Dose: 50 mg, 2 times / day
Route: oral
Route: multiple
Dose: 50 mg, 2 times / day
Sources: Page: p.2447
unhealthy, ADULT
n = 25
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: FASTED
Population Size: 25
Sources: Page: p.2447
DLT: Pruritic rash...
Dose limiting toxicities:
Pruritic rash (grade 2, 8%)
Sources: Page: p.2447
60 mg 1 times / day multiple, oral
MTD
Dose: 60 mg, 1 times / day
Route: oral
Route: multiple
Dose: 60 mg, 1 times / day
Sources: Page: p.4
unhealthy, ADULT
n = 15
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 15
Sources: Page: p.4
90 mg 1 times / day multiple, oral
MTD
Dose: 90 mg, 1 times / day
Route: oral
Route: multiple
Dose: 90 mg, 1 times / day
Sources: Page: p.2448
unhealthy, ADULT
n = 19
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: FASTED
Population Size: 19
Sources: Page: p.2448
DLT: Skin rash, Electrocardiogram T wave inversion...
Dose limiting toxicities:
Skin rash (grade 3, 5.3%)
Electrocardiogram T wave inversion (grade 3, 5.3%)
Sources: Page: p.2448
100 mg 1 times / day multiple, oral
Studied dose
Dose: 100 mg, 1 times / day
Route: oral
Route: multiple
Dose: 100 mg, 1 times / day
Sources: Page: p.2447
unhealthy, ADULT
n = 7
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: FASTED
Population Size: 7
Sources: Page: p.2447
DLT: Skin rash, Dyskinesia...
Dose limiting toxicities:
Skin rash (grade 3, 14.3%)
Dyskinesia (grade 2, 14.3%)
Sources: Page: p.2447
50 mg 2 times / day multiple, oral
Studied dose
Dose: 50 mg, 2 times / day
Route: oral
Route: multiple
Dose: 50 mg, 2 times / day
Sources: Page: p.4
unhealthy, ADULT
n = 6
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 6
Sources: Page: p.4
DLT: Macular rash, Maculopapular rash...
Dose limiting toxicities:
Macular rash (grade 3, 16.7%)
Maculopapular rash (grade 3, 16.7%)
Sources: Page: p.4
70 mg 1 times / day multiple, oral
Studied dose
Dose: 70 mg, 1 times / day
Route: oral
Route: multiple
Dose: 70 mg, 1 times / day
Sources: Page: p.4
unhealthy, ADULT
n = 6
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 6
Sources: Page: p.4
DLT: Fatigue...
Dose limiting toxicities:
Fatigue (grade 3, 33.3%)
Sources: Page: p.4
AEs

AEs

AESignificanceDosePopulation
Hepatic enzyme increased 42.9%
120 mg 2 times / day multiple, oral
Highest studied dose
Dose: 120 mg, 2 times / day
Route: oral
Route: multiple
Dose: 120 mg, 2 times / day
Sources: Page: p.2447
unhealthy, ADULT
n = 7
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: FASTED
Population Size: 7
Sources: Page: p.2447
Decreased appetite grade 3, 14.3%
DLT
120 mg 2 times / day multiple, oral
Highest studied dose
Dose: 120 mg, 2 times / day
Route: oral
Route: multiple
Dose: 120 mg, 2 times / day
Sources: Page: p.2447
unhealthy, ADULT
n = 7
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: FASTED
Population Size: 7
Sources: Page: p.2447
Hypophosphatemia grade 3, 14.3%
DLT
120 mg 2 times / day multiple, oral
Highest studied dose
Dose: 120 mg, 2 times / day
Route: oral
Route: multiple
Dose: 120 mg, 2 times / day
Sources: Page: p.2447
unhealthy, ADULT
n = 7
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: FASTED
Population Size: 7
Sources: Page: p.2447
Fatigue grade 3, 16.7%
DLT
40 mg 2 times / day multiple, oral
MTD
Dose: 40 mg, 2 times / day
Route: oral
Route: multiple
Dose: 40 mg, 2 times / day
Sources: Page: p.4
unhealthy, ADULT
n = 6
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 6
Sources: Page: p.4
Pruritic rash grade 2, 8%
DLT
50 mg 2 times / day multiple, oral
MTD
Dose: 50 mg, 2 times / day
Route: oral
Route: multiple
Dose: 50 mg, 2 times / day
Sources: Page: p.2447
unhealthy, ADULT
n = 25
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: FASTED
Population Size: 25
Sources: Page: p.2447
Electrocardiogram T wave inversion grade 3, 5.3%
DLT
90 mg 1 times / day multiple, oral
MTD
Dose: 90 mg, 1 times / day
Route: oral
Route: multiple
Dose: 90 mg, 1 times / day
Sources: Page: p.2448
unhealthy, ADULT
n = 19
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: FASTED
Population Size: 19
Sources: Page: p.2448
Skin rash grade 3, 5.3%
DLT
90 mg 1 times / day multiple, oral
MTD
Dose: 90 mg, 1 times / day
Route: oral
Route: multiple
Dose: 90 mg, 1 times / day
Sources: Page: p.2448
unhealthy, ADULT
n = 19
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: FASTED
Population Size: 19
Sources: Page: p.2448
Dyskinesia grade 2, 14.3%
DLT
100 mg 1 times / day multiple, oral
Studied dose
Dose: 100 mg, 1 times / day
Route: oral
Route: multiple
Dose: 100 mg, 1 times / day
Sources: Page: p.2447
unhealthy, ADULT
n = 7
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: FASTED
Population Size: 7
Sources: Page: p.2447
Skin rash grade 3, 14.3%
DLT
100 mg 1 times / day multiple, oral
Studied dose
Dose: 100 mg, 1 times / day
Route: oral
Route: multiple
Dose: 100 mg, 1 times / day
Sources: Page: p.2447
unhealthy, ADULT
n = 7
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: FASTED
Population Size: 7
Sources: Page: p.2447
Macular rash grade 3, 16.7%
DLT
50 mg 2 times / day multiple, oral
Studied dose
Dose: 50 mg, 2 times / day
Route: oral
Route: multiple
Dose: 50 mg, 2 times / day
Sources: Page: p.4
unhealthy, ADULT
n = 6
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 6
Sources: Page: p.4
Maculopapular rash grade 3, 16.7%
DLT
50 mg 2 times / day multiple, oral
Studied dose
Dose: 50 mg, 2 times / day
Route: oral
Route: multiple
Dose: 50 mg, 2 times / day
Sources: Page: p.4
unhealthy, ADULT
n = 6
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 6
Sources: Page: p.4
Fatigue grade 3, 33.3%
DLT
70 mg 1 times / day multiple, oral
Studied dose
Dose: 70 mg, 1 times / day
Route: oral
Route: multiple
Dose: 70 mg, 1 times / day
Sources: Page: p.4
unhealthy, ADULT
n = 6
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 6
Sources: Page: p.4
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG



OverviewOther

Other InhibitorOther SubstrateOther Inducer


Drug as perpetrator​
PubMed

PubMed

TitleDatePubMed
Patents

Sample Use Guides

50 mg twice daily: no eating for 2 hours prior and 1 hour after dose
Route of Administration: Oral
Voxtalisib treatment results in decreased cell viability in 13 PDA cell lines in a dose-dependent manner. 10uM induced approx. 40% apoptosis in BxPC-3 cells.
Substance Class Chemical
Created
by admin
on Sat Jun 26 04:15:07 UTC 2021
Edited
by admin
on Sat Jun 26 04:15:07 UTC 2021
Record UNII
CVL1685GPH
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
VOXTALISIB
INN   USAN   WHO-DD  
USAN   INN  
Official Name English
SAR-245409
Code English
SAR245409
Code English
PYRIDO(2,3-D)PYRIMIDIN-7(8H)-ONE, 2-AMINO-8-ETHYL-4-METHYL-6-(1H-PYRAZOL-3-YL)-
Systematic Name English
XL-765
Code English
2-AMINO-8-ETHYL-4-METHYL-6-(1H-PYRAZOL-3-YL)PYRIDO(2,3-D)PYRIMIDIN-
Systematic Name English
2-AMINO-8-ETHYL-4-METHYL-6-(1H-PYRAZOL-5-YL)PYRIDO(2,3-D)PYRIMIDIN-7(8H)-ONE
Systematic Name English
VOXTALISIB [INN]
Common Name English
VOXTALISIB [USAN]
Common Name English
XL765
Code English
VOXTALISIB [WHO-DD]
Common Name English
2-AMINO-8-ETHYL-4-METHYL-6-(1H-PYRAZOL-3-YL)PYRIDO(2,3-D)PYRIMIDIN-7(8H)-ONE
Systematic Name English
Classification Tree Code System Code
NCI_THESAURUS C129825
Created by admin on Sat Jun 26 04:15:07 UTC 2021 , Edited by admin on Sat Jun 26 04:15:07 UTC 2021
NCI_THESAURUS C2152
Created by admin on Sat Jun 26 04:15:07 UTC 2021 , Edited by admin on Sat Jun 26 04:15:07 UTC 2021
Code System Code Type Description
FDA UNII
CVL1685GPH
Created by admin on Sat Jun 26 04:15:07 UTC 2021 , Edited by admin on Sat Jun 26 04:15:07 UTC 2021
PRIMARY
EVMPD
SUB184196
Created by admin on Sat Jun 26 04:15:07 UTC 2021 , Edited by admin on Sat Jun 26 04:15:07 UTC 2021
PRIMARY
NCI_THESAURUS
C71704
Created by admin on Sat Jun 26 04:15:07 UTC 2021 , Edited by admin on Sat Jun 26 04:15:07 UTC 2021
PRIMARY
DRUG BANK
DB12400
Created by admin on Sat Jun 26 04:15:07 UTC 2021 , Edited by admin on Sat Jun 26 04:15:07 UTC 2021
PRIMARY
PUBCHEM
16123056
Created by admin on Sat Jun 26 04:15:07 UTC 2021 , Edited by admin on Sat Jun 26 04:15:07 UTC 2021
PRIMARY
CAS
934493-76-2
Created by admin on Sat Jun 26 04:15:07 UTC 2021 , Edited by admin on Sat Jun 26 04:15:07 UTC 2021
PRIMARY
ChEMBL
CHEMBL3545366
Created by admin on Sat Jun 26 04:15:07 UTC 2021 , Edited by admin on Sat Jun 26 04:15:07 UTC 2021
PRIMARY
INN
9709
Created by admin on Sat Jun 26 04:15:07 UTC 2021 , Edited by admin on Sat Jun 26 04:15:07 UTC 2021
PRIMARY
CAS
1123889-87-1
Created by admin on Sat Jun 26 04:15:07 UTC 2021 , Edited by admin on Sat Jun 26 04:15:07 UTC 2021
SUPERSEDED
Related Record Type Details
ACTIVE MOIETY